(harbor) study to evaluate efficacy and safety of blu-263 versus placebo in patients with indolent systemic mastocytosis

Conditions: Indolent Systemic Mastocytosis; Smoldering Systemic Mastocytosis

Summary: this is a randomized, double-blind, placebo-controlled, phase 2/3 study comparing the efficacy and safety of elenestinib (blu-263) + symptom directed therapy (sdt) with placebo + sdt in participants with indolent systemic mastocytosis (ism) whose symptoms are not adequately controlled by sdt. parts 1 and 2 will enroll participants with ism. participants enrolled in part 2 will roll over onto part 3 to receive treatment with elenestinib in an open-label fashion following completion of the earlier part. part k will enroll participants with ism who have previously received an approved selective kit inhibitor. the study also includes pharmacokinetic (pk) groups that will enroll participants with ism.


Eligibility criteria:
key inclusion criteria: all participants: -participant must have an eastern cooperative oncology group performance status (ecog ps) of 0 to 2. part 1 and pk groups: * participant has confirmed diagnosis of ism, confirmed by central pathology review * participant must have failed to achieve adequate symptom control for 1 or more baseline symptoms, as determined by the investigator, with at least 2 of the following symptom-directed therapies administered: h1 blockers, h2 blockers, proton-pump inhibitors, leukotriene inhibitors, cromolyn sodium, corticosteroids, or omalizumab. * participants must have sdt for ism symptom management stabilized for at least 14 days prior to starting screening procedures. * for participants receiving corticosteroids, the dose must be ≤ 20 mg/day prednisone or equivalent, and the dose must be stable for ≥ 14 days. part k: -participant has confirmed diagnosis of ism, confirmed by central pathology review part s: -participant has confirmed diagnosis of ssm, confirmed by central pathology review of bm biopsy and central review of b- and c-findings by who diagnostic criteria. part 2: -participant has confirmed diagnosis of ism, confirmed by central pathology review key exclusion criteria: * participant has been diagnosed with any of the following who systemic mastocytosis (sm) sub-classifications: cutaneous mastocytosis only, sm with an associated hematologic neoplasm of non-mc lineage (sm-ahn), aggressive sm, mast cell leukemia, or mast cell sarcoma. * participant has been diagnosed with another myeloproliferative disorder. * participant has organ damage attributable to sm. * participant has clinically significant, uncontrolled, cardiovascular disease * participant has a qt interval corrected using fridericia's formula (qtcf) \> \> 470 milliseconds (msec) (for females) or \> 450 msec (for males). * participant has a history of a primary malignancy that has been diagnosed or required therapy within 3 years. the following prior malignancies are not exclusionary: completely resected basal cell and squamous cell skin cancer, curatively treated localized prostate cancer, and completely resected carcinoma in situ of any site. * time since any cytoreductive therapy including masitinib and midostaurin should be at least 5 half-lives or 14 days (whichever is longer), and for cladribine, interferon alpha, pegylated interferon, or antibody therapy \< 28 days or 5 half-lives of the drug (whichever is longer), before beginning the screening period. * participant has received radiotherapy or psoralen and ultraviolet a (puva) therapy \< 14 days before beginning the screening period. other protocol-defined criteria apply.

Keywords: ism ssm